1. Field of the Invention
The present invention relates to a new prostaglandin compounds and more particularly new 15-dehydroxy-16-oxoprostaglandins.
Prostaglandins (hereinafter, prostaglandin is referred to as PG) are members of a class of organic carboxylic acids that are contained in human and most other mammalian tissues or organs and that exhibit a wide range of physiological activities. Naturally occurring PGs possess as a common structural feature the prostanoic acid skeleton: ##STR2## Some synthetic analogues have somewhat modified skeletons. On the basis of the structural features of their five-membered ring moiety, the PGs are classified into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs and PGJs. These are further classified based on whether or not there are unsaturated groups and oxidized groups in the chain moiety as:
Subscript 1 - - - 13,14-unsaturated-15-OH PA1 Subscript 2 - - - 5,6-- and 13,14-diunsaturated-15-OH PA1 Subscript 3 - - - 5,6- 13,14- and 17,18-triunsaturated-15-OH PA1 X.sub.1 and X.sub.2 are hydrogen atom, halogen atom or lower alkyl, PA1 Y is --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, --C.tbd.C-- or --CO--CH.sub.2 --, PA1 Z is --CH.sub.2 --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--CH.sub.2 -- or --CH.sub.2 --CH.dbd.CH--, PA1 R.sub.1 is hydrogen atom, lower alkyl, lower cycloalkyl, monocyclic aryl, monocyclic aryl(lower)alkyl or monocyclic aroyl(lower)alkyl, PA1 R.sub.2 is single bond or lower alkylene, PA1 R.sub.3 is lower alkyl which is unsubstituted or substituted with halogen, lower cycloalkyl which is unsubstituted or substituted with lower alkyl, monocyclic aryl which is unsubstituted or substituted with halogen or halo(lower)alkyl, or monocyclic aryloxy which is unsubstituted or substituted with halogen or halo(lower)alkyl,
In the above formula (A), for example, PGEs are compounds which have an oxo group at position 9 and a hydroxy group at position 11. PGFs are compounds which have hydroxy groups at positions 9 and 11. PGDs are compounds which have a hydroxy group at position 9 and an oxo group at position 11. PGAs are compound which have an oxo group at position 9, a hydrogen atom at position 11 and a double bond between positions 10 and 11. It has been known that PGs have various physiological activities such as anti-ulcerous, uterine-contractile, intestine-contractile, vasodilating, and diarrheic activities.
It is also known that the natural PGs are chemically unstable and very rapidly metabolized in the living body.
Compounds having an oxo group in place of a hydroxy group at position 15 of the prostanoic acid skeleton and their derivatives have also been described (for example, JP-A-52753/1989, JP-A-104040/1989 and JP-A-151552/1989).
While the fact that a compound has various activities appears to be advantageous at first sight, the presence of activities which are not useful in individual cases is not desirous because they are disliked as side-effects. Therefore, it is desirous to develop compounds having only one particular activity or a limited number of activities out of various activities of PGs. Furthermore, there is a continuous demand for the compounds of this kind which have improved chemical stability and reduced rate of metabolic degradation in the living body in comparison with the natural PGs. The compounds according to the invention have been successfully synthesized as a result of extensive study seeking for such compounds.